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Endocrine Abstracts (2018) 59 OC3.1 | DOI: 10.1530/endoabs.59.OC3.1

1Section of Endocrinology and Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, London, UK; 2Department of Endocrinology, Imperial College Healthcare NHS Trust, London, UK; 3Section of Metabolic Medicine, Imperial College London, St Mary’s Hospital, London, UK; 4Statsconsultancy Ltd, 40 Longwood Lane, Amersham, UK; 5National Phenotyping Centre, Imperial College London, Hammersmith Hospital, London, UK; 6Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine Imperial College London, London, UK; 7Imperial Pancreatic Islet Biology and Diabetes Consortium, Hammersmith Hospital, Imperial College London, London, UK; 8Diabetes Research Institute (HSR-DRI), San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy; 9Vita-Salute San Raffaele University, Milan, Italy; 10Department of Clinical and Experimental Medicine, Islet Cell Laboratory, University of Pisa, Pisa, Italy; 11Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK; 12Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Oxford, UK; 13National Institute of Health Research Oxford Biomedical Research Centre, Churchill Hospital, Oxford, UK; 14Clinical Islet Laboratory and Clinical Islet Transplant Program, University of Alberta, Alberta, Canada.

Background: Limited data exists on the hormonal mediators connecting metabolism and reproduction. Animal studies show that the reproductive hormone, kisspeptin, may also be important in metabolism. We investigated the effects of kisspeptin on human metabolism for the first time, to explore possible kisspeptin-mediated links between reproduction and metabolism.

Methods: We performed intravenous glucose tolerance tests (IVGTTs) in 15 healthy men (age 25±1y, BMI 22.3±0.5 kg.m−2); during 1−−1 kisspeptin infusion and vehicle infusion. Blood samples were collected pre- and during infusions (pre-glucose load/pre-meal), when kisspeptin levels had plateaued, to determine kisspeptin’s effects on serum metabolites. Static incubation experiments were performed using human donor islet cells (n=6) and a human pancreatic β-cell line (EndoC-βH1 cells), to assess in vitro effects of kisspeptin on glucose-stimulated insulin secretion (GSIS).

Results: During IVGTTs, GSIS was higher with kisspeptin infusion compared to vehicle (mean serum insulin concentration kisspeptin minus vehicle: 4.1 μU.mL−1, P=0.01; disposition index: kisspeptin 2768±484 vs vehicle 2061±255, P<0.05). Consistent with this and providing mechanistic information, kisspeptin elicited dose-dependent increases in insulin secretion in vitro, in human islet and EndoC-βH1 cells. Compared to vehicle, kisspeptin resulted in changes in serum metabolites, including alterations in lysophosphatidylcholines, phosphocholines and sphingomyelins, which are associated with insulin secretion.

Conclusions: This is the first study to examine the effects of kisspeptin on metabolism in vivo in humans. We demonstrate that kisspeptin increases GSIS and produces changes in circulating metabolites, providing evidence for novel kisspeptin-mediated connections between reproduction and metabolism. This has significant implications for the ongoing development of kisspeptin-based therapies: in addition to treating reproductive disorders kisspeptin may also have positive effects on associated metabolic dysfunction (for example in men with type 2 diabetes, up to 40% of whom have associated hypogonadism).

Volume 59

Society for Endocrinology BES 2018

Glasgow, UK
19 Nov 2018 - 21 Nov 2018

Society for Endocrinology 

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